Treatment of large cold benign thyroid nodules not eligible for surgery with percutaneous ethanol injection

We studied the effect of percutaneous ethanol injection (PEI) in the treatment of cold, cytologically benign, large (>10 mL) thyroid nodules (CBNs) in 41 patients. The end-point of our study was to evaluate the efficacy of PEI on: 1) local symptomatology, assessed by an arbitrary symptom score; and 2) nodule volume and tracheal displacement (at ultrasonography). Follow-up ranged from 12-36 (21 +/- 9) months. Symptom score was significantly reduced (P < 0.01) after 6 months and at the end of the follow-up (2.1 +/- 0.3 vs. 0.2 +/- 0.5 and vs. 0.2 +/- 0.4). A significant (P < 0.01) nodule volume reduction was observed, without differences between solid or mixed CBNs; the reduction was 50% or more in 92.7% of patients. Neither clinical parameters nor pretreatment nodule ultrasonographic features were related to nodule reduction. Disappearance or significant reduction (>0.5 cm) of tracheal displacement was obtained in 61% and in 39% of patients, respectively. One patient experienced prethyroid region edema, pain, and mild fewer, which reversed within 1 week; and one patient had dysphonia, caused by vocal cord palsy, which reversed spontaneously within 1 month. At the end of the follow-up, nodules with just necrotic material at cytology showed a greater (P < 0.05) volume reduction than nodules with residual benign thyroid cells. Our data suggest that PEI is a safe and effective treatment of large CBNs, although sometimes serious side effects do occur.     

A conserved TN8TCCT motif in the octapeptide-encoding region of Pax genes which has the potential to direct cytosine methylation

Our previous findings have shown that the developmental genes Pax7 and Pax3 are differentially methylated; the gene region that encodes the paired domain is hypomethylated, whereas the region that encodes the homeodomain is hypermethylated. For this reason, the known DNA sequence between the paired and homeoboxes was analysed for the presence of a conserved DNA motif to which a modifying protein could bind in order to direct the methylation or demethylation of surrounding gene sequences. The octapeptide-encoding region was found to contain several nucleotides that were highly conserved throughout the Pax gene family from phylogenetically distant species. The most conserved nucleotides are thought to comprise a motif TN8TCCT where N8=any combination of eight nucleotides. A conserved octapeptide-like-encoding sequence containing the TN8TCCT motif was also found in non-Pax genes of higher eukaryotes and in the non-coding strand of plants. Moreover, differential methylation seems to be associated with the presence of the TN8TCCT motif in p53 and the human oestrogen receptor genes. The presence of the TN8TCCT motif within an octapeptide-like-encoding sequence in human T-cell leukaemia virus type 1 might suggest that the putative recognition motif may have been introduced into various host genomes via some form of retroviral agent.     

The success of locoregional, low-dose recombinant interleukin-2 therapy in tumor-bearing mice is dependent on the time of rIL-2 administration

The most common chromosomal aberrations in myelodysplastic syndromes (MDS) are complete or partial loss of chromosomes 5 and 7, and trisomy 8. To identify genes important in the pathogenesis of this disease that could be associated with these gross chromosomal defects, we have employed the differential display PCR (DDPCR) procedure developed by Liang and Pardee. This method allows simultaneous comparison of several cDNA sources for the presence of differentially expressed genes. Polymorphonuclear cells (PMNs) from two MDS patients, containing a 5q deletion or a trisomy 8, and three healthy controls were used. Initial screening resulted in the identification of five and three partial cDNA sequences, respectively that were either differentially expressed in both patient samples or in individual patients, as compared with the controls. The authenticity of aberrant expression was verified by reanalyzing the same primer combinations on newly prepared cDNA. Differential expression of the three remaining fragments was subsequently checked on a larger panel of MDS patients, using amplicon-specific primer sets. These were obtained by cloning and sequencing of the fragments. For one partial cDNA (DC3), the original expression pattern, i.e., decreased expression in individual MDS patients, was confirmed. These results demonstrate the utility of the DDPCR procedure to isolate differentially expressed sequences in primary patient samples where the availability of cells is a limiting factor.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

The psychosomatic network: foundations of mind-body medicine

Research in the 1980s uncovered ubiquitous neuropeptide-receptor distribution in brain structures associated with emotional processing, and throughout many organ systems. This finding supported neuropeptides as biochemical substrates of emotion, and the neuropeptide-receptor network as a parasynaptic system crossing traditional brain-body boundaries. The medical relevance of these findings was affirmed by psychoneuroimmunology research: neuropeptides help to regulate immunocyte trafficking, there is bidirectional communication between nervous and immune system components, immunocytes produce neuropeptides, and nerve cells produce immune-associated cytokines. In the past decade, the concept of a unified psychosomatic network has been strengthened by animal and human research demonstrating relationships between behavior and neuropeptide-mediated regulation of immune functions. Research on emotional expression or disclosure in healthy human subjects as well as in cancer and HIV-positive patients has shown significant positive correlations with clinically relevant immune functions and/or positive health outcomes. Psychosocial interventions emphasizing emotional expression or active coping have evidenced survival benefits in breast cancer and melanoma. These findings suggest that emotional expression generates balance in the neuropeptide-receptor network and a functional healing system. Emotional expression is also a marker for psychospiritual vitalization, and further research should evaluate links between energy-based models of health and neuropeptide-receptor-based models under the rubric of an informational paradigm.     

An improved theory for the prediction of microcavitation thresholds

An approximate analytical formulation is presented that allows for the calculation of acoustic pressure thresholds for transient cavitation over a variety of frequencies and host fluid parameters. Specifically, R.E. Apfel's (1986) theory is extended to include an estimate of the time delay associated with the Laplace pressure, 2sigma/R(0), where sigma is the surface tension and R(0) is the initial radius. Also presented is a correction factor for the time-averaged pressure difference, across the bubble wall during growth. An optimum size distribution of nuclei for the predisposition of a sample to microcavitation is exhibited. The role of transient cavitation in medical ultrasound is discussed.     

Amino acid profiles and liposomes: Their role as chemosensory information carriers in the marine environment

Yellowfin tuna enhance their hunting success in the vast pelagic environment by using their sense of smell to detect intact (uninjured) prey that are beyond visual range. However, the olfactory cues that tuna use would normally face huge and rapid dilution in the open ocean. We demonstrate that these prey odors are complexed within biologically derived lipid structures that probably delay the dilution of the amino acids to subthreshold concentrations and provide persistent arousal and search cues for the tuna. This may be the first demonstration of an extracorporeal biological function for liposomes. Tuna may also form chemical search images to maximize feeding efficiency. We demonstrate that the amino acid profiles of various prey species are consistent over time and between schools, which makes the formation of search images feasible.     

A modification of broyden's method for the solution of sparse systems—with application to distillation problems described by nonideal thermodynamic functions

An algorithm that permits Broyden's method to be used for the solution of large systems of algebraic equations with sparse Jacobians is presented. The new procedure is compared to Schubert's modification of Broyden's method and to the Newton-Raphson method by solving an extractive distillation problem. It is demonstrated that the new procedure is competitive with Schubert's method when it is necessary to evaluate Jacobian matrices numerically.     

Determination of Both Mesopores and Macropores in Three-Dimensional Ordered Porous Materials by Nitrogen Adsorption

Three-dimensionally ordered silica structures containing both mesopores and macropores are created using polystyrene coacervate spheres with a diameter of ca. 146 nm. The close-packed polystyrene coacervate spheres are intercalated with tetraethyl orthosilicate. The spheres are removed by calcination leaving an inverse silica replica with a spherical macropore cavity diameter of 110 nm. Due to the nature of these porous structures, pores leading into the macropore cavity are in the mesopore regime, 40 nm in diameter. The nitrogen adsorption data described in the following paper gives a pore size for both the macropore cavity and the mesopore openings leading into the cavity. The pore sizes as determined by nitrogen sorption are in good agreement with the pore sizes observed by scanning electron microscopy. Mercury intrusion porosimetry results confirm the size of the mesopore openings leading into the macropore cavity, however due to destruction of the sample upon intrusion, extrusion results can not be obtained to determine main cavity diameters. As a result, nitrogen sorption may be a viable option for determining pore sizes with these three-dimensionally ordered materials containing both mesopores and macropores.